The Value of Anti-drug Antibody Detection in Discriminating Patients  from Healthy Controls and Predicting the Gross Motor Functional State  in Patients with Pompe Disease

Solmaz  Aziz-Ahari; Mahdi  Aminian; Aliasghar  Rahimian; Shahriar  Nafissi; Morteza  Heidari; Ali  Rabbani; Amir-Hassan  Zarnani; Ali  Mohebbi; Reza Shervin  Badv; Nargess  Saladjegheh; Sahar  Mortezagholi; Safdar  Masoumi; Zahra  Hadipour; Reza  Boostani; Mehran  Beiraghi Toosi; Keyhan  Sayadpour Zanjani; Ali  Khajeh; Seyed Hassan  Tonkaboni; Maryam  Sadeghi; Farzad  Fatehi; Elahe  Vafaei; Mahmoud Reza  Ashrafi

doi:10.18502/ijaai.v25i2.20800

Solmaz Aziz-Ahari Division of Pediatric Neurology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Mahdi Aminian Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Aliasghar Rahimian Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Shahriar Nafissi Neuromuscular Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Morteza Heidari Division of Pediatric Neurology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Ali Rabbani Growth and Development Research Center, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Amir-Hassan Zarnani Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Ali Mohebbi Growth and Development Research Center, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Reza Shervin Badv Division of Pediatric Neurology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Nargess Saladjegheh Medical Laboratory, Social Security Organization, Tehran, Iran
Sahar Mortezagholi Department of Immunology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Safdar Masoumi Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Zahra Hadipour Department of Clinical Genetics, Atieh Hospital, Tehran, Iran
Reza Boostani Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Mehran Beiraghi Toosi Department of Pediatric Neurology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
Keyhan Sayadpour Zanjani Division of Cardiology, Department of Pediatric, Pediatric Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Ali Khajeh Department of Pediatric Neurology, Children and Adolescents Health Research Center, Zahedan University of Medical Science, Zahedan, Iran
Seyed Hassan Tonkaboni Department of Pediatric Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Maryam Sadeghi Division of Pediatric Neurology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Farzad Fatehi Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Elahe Vafaei Fetal and Pediatric Cardiovascular Research Center, Pediatric Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Mahmoud Reza Ashrafi Division of Pediatric Neurology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v25i2.20800

Keywords: Anti-rhGAA antibody; ELISA; Enzyme replacement therapy; Motor function; Pompe disease; Western blot

Abstract

Anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody formation is a major challenge in patients with Pompe disease receiving enzyme replacement therapy (ERT). The clinical significance of these antibodies and their detection methods remain uncertain. This study aimed to evaluate the diagnostic and functional relevance of anti-rhGAA antibodies in late- onset Pompe
disease (LOPD) and to compare the performance of ELISA and Western blot assays.

Fourteen patients with LOPD undergoing ERT and 14 age- and sex-matched healthy controls were studied. Serum anti-rhGAA antibodies and their IgG, IgM, and IgA isotypes were quantified using ELISA and verified by Western blot. Motor function was assessed using the Pompe Motor Function Levels Questionnaire, an adapted version of the GMFCS validated for Pompe disease.

Total and isotype-specific anti-rhGAA antibody levels were significantly higher in patients than in controls. ROC analysis showed excellent discrimination between groups. Strong agreement was observed between ELISA and Western blot results. However, antibody levels were not significantly correlated with motor function grade. Given the small sample size (n=14), this non-significant result may reflect limited statistical power rather than a true lack of association.

Anti-rhGAA antibody detection effectively distinguishes LOPD patients from healthy individuals. Western blot provides a reliable, low-cost alternative to ELISA, particularly useful in resource-limited settings. Nevertheless, the prognostic utility of antibody titers for functional outcomes remains uncertain and warrants larger, multicenter validation studies.